Cyclohexane ring reversal

When viewing cyclohexane, it s helpful to remember that the lower bond is in front and the upper bond is in back. If this convention is not defined, an optical illusion can make it appear that the reverse is true. For clarity, all cyclohexane rings drawn in thisbook will have the front (lower) bond heavily shaded to indicate nearness to the viewer. 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

Axial-equatorial interconversion through ring reversal has been studied in a wide variety of systems in addition to cyclohexane, including heterocycles such as piperidine (5-9), unsaturated rings [e.g., cyclohexene (5-10)], fused rings like cw-decalin (5-11), and... 

Ring inversion (ring reversal) The interconversion of cyclohexane conformations having similar shapes (chair - chair), accompanied by interchange of the equatorial and axial substituents. Similarly, the interchange of any such similarly shaped conformations in a cyclic molecule. 

The two reactions above illustrate two important ways of making an epoxide. We are now going to look in a little more detail at what happens when epoxides are opened—a reaction that is essentially the reverse of the epoxide-closing reaction you have just seen. Here are both reactions with the epoxide fused to a cyclohexane ring ... 

In practice, the rules are complex and it is not correct simply to say that all cyclohexane rings will have the above effects. In the case where the cyclohexane ring is in a terminal function then the reverse effect can be observed. For example the N I transitions in the benzoate esters are lower than those in the corresponding raro-cyclohexane carboxylic esters. ... 

In 1955, Corey and Burke published an article discussing conformational studies with 2-chlorocyclohexanone, similar to those reported earlier for the corresponding bromoketone. It had been anticipated that the amount of axial isomer would be greater in the chloro compound than in the bromo. The C-Cl and C-Br dipoles are similar, so the electrostatics in the two cases should be similar. But because the axial position is crowded in a cyclohexane ring, the smaller chlorine atom was expected to fit there more easily than the bromine. However, the reverse was found to be true. Subsequent experimental studies showed that this is part of a steady progression from fluorine through bromine, where the percentage axial conformer in the equiUbrium increases steadily and appreciably as we go down the periodic table. 

Substituent effects (electronegativity, configuration) influence these coupling constants in four-, five- and seven-membered ring systems, sometimes reversing the cis-tmns relationship so that other NMR methods of structure elucidation, e.g. NOE difference spectra (see Section 2.3.5), are needed to provide conclusive results. However, the coupling constants of vicinal protons in cyclohexane and its heterocyclic analogues (pyranoses, piperidines) and also in alkenes (Table 2.10) are particularly informative. 

---